Study on the Inhibitory Effects of Naringenin-Loaded Nanostructured Lipid Carriers Against Nonalcoholic Fatty Liver Disease.

Naringenin (NGN) can be used to inhibit the progression of nonalcoholic fatty liver disease (NAFLD) in mice, but its poor water solubility limits its applications. Nanostructured lipid carriers (NLCs) have recently attracted much attention in the field of nanodrug delivery systems because they increase the drug loading capacity and impressively enhance the solubility of indissolvable drugs. Herein, a thin-film dispersion method was used to prepare naringenin-loaded nanostructured lipid carriers (NGN-NLCs). These NGN-NLCs have a narrow size distribution of 171.9 ±2.0 nm, a high drug loading capacity of 23.7 ± 0.3%, a high encapsulation efficiency of 99.9 ± 0.0% and a drug release rate of 86.2 ± 0.4%. NGN- NLCs elevated the pharmacokinetic parameters (Cmax and AUC0→t) of NGN, accelerated NGN transepithelial transport in MDCK cells and intestinal absorption in the jejunum and ileum, and reduced hepatic lipid accumulation in an oleic acid (OA) plus lipopolysaccharide (LPS)-induced lipid deposition cell model in primary hepatocytes and in a methionine/choline deficient (MCD) diet-induced NAFLD mouse model. A detailed study of the mechanism showed that this NLC formulation elevated the drug release rate in simulated intestinal solutions in vitro, the transepithelial transport in MDCK cells, the oral absorption in mice and the ex vivo intestinal absorption of NGN. Thus, NGN-NLCs significantly enhanced the inhibitory effects of NGN on MCD diet induced mouse NAFLD.